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Results for “Likelihood Functions”

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PubMed1993

A comparison of univariate and multivariate tests for genetic linkage.

A variety of robust and model-dependent genetic linkage methods were applied to log transformed lipid levels from a large pedigree in which the LDL receptor defect has been shown to segregate by molecular biologic techniques. Application of the Haseman-Elston and a variance-components based test for linkage identified LDL and cholesterol as cosegregating with the marker C3, which is genetically linked to the LDL receptor defect. Consideration of lipid fractions as a multivariate response identified (0.723 x cholesterol) - (0.551 x triglycerides) as most strongly supporting evidence for linkage with C3. Subsequent segregation and linkage analyses provided support for an autosomal dominant major gene influencing either LDL or the function of cholesterol and triglycerides. Genetic linkage to LDL was only mildly supported, with a maximum lod score of 0.51 at a recombination fraction of theta = 0.33. Genetic linkage of the linear function to C3 was more strongly supported, with a maximum lod score of 1.69 at theta = 0.09. Bivariate analysis of clinical affection (with either type IIa or type IIb hyperlipidemia) and quantitative measures (LDL or the linear function) generally led to decreased lod scores, indicating, in this pedigree, loss of information when using clinical affection.

Chromosome Aberrations↗

PubMed2006

Drosophila mojoless, a retroposed GSK-3, has functionally diverged to acquire an essential role in male fertility.

Retroposition is increasingly recognized as an important mechanism for the acquisition of new genes. We show that a glycogen synthase kinase-3 gene, shaggy (sgg), retroposed at least 50 MYA in the Drosophila genus to generate a new gene, mojoless (mjl). We have extensively analyzed the function of mjl and examined its functional divergence from the parental gene sgg in Drosophila melanogaster. Unlike Sgg, which is expressed in many tissues of both sexes, Mjl is expressed specifically in the male germ line, where it is required for male germ line survival. Our analysis indicates that mjl has acquired a specific function in the maintenance of male germ line viability. However, it has not completely lost its ancestral biochemical function and can partially compensate for loss of the parental gene sgg when ectopically expressed in somatic cells. We postulate that mjl has undergone functional diversification and is now under stabilizing selection in the Drosophila genus.

Amino Acid Sequence↗

PubMed1998

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

AIDS Dementia Complex↗

PubMed2002

Breathing easy: a prospective study of optimism and pulmonary function in the normative aging study.

Although there is good evidence that emotions are associated with chronic airways obstruction, evidence for the influence of psychological factors on the level and decline of pulmonary function is sparse. Optimism has been linked to enhanced well-being, whereas pessimism has been identified as a risk factor for poor physical health. This investigation examines prospectively the effects of optimism versus pessimism on pulmonary function. Data are from the Veterans Administration Normative Aging Study, an ongoing cohort of older men. In 1986, 670 men completed the revised Minnesota Multiphasic Personality Inventory from which we derived the bipolar Revised Optimism-Pessimism Scale. During an average of 8 years of follow-up, an average of 3 pulmonary function exams were obtained. Men with a more optimistic explanatory style had significantly higher levels of forced expiratory volume in 1 sec (FEV1) and forced vital capacity (both p < .01). Interactions between time and optimism suggested that rate of decline in FEV1 over time was slower in men with a more optimistic explanatory style relative to men who were more pessimistic. These data are the first to link optimism with higher levels of pulmonary function and slower rate of pulmonary function decline in older men, a protective effect that is independent of smoking.

Adult↗

PubMed1999

A comparison of three polytomous item response theory models in the context of testlet scoring.

An alternative to dichotomous scoring of multiple items anchored to a common stem is scoring these items as a single polytomous item (testlet scoring). This study systematically compared the partial credit model (PCM), the generalized partial credit model (GPCM), and the graded response model (GRM) in the context of testlet scoring. Data sets included a sample from the fall 1994 administration of the SAT I (N = 2,548) and a simulated data set. Theta estimation, information, and model fit were analyzed. Correlations among theta estimates ranged from 0.9748 to 0.9921. The relationship among the information functions of the PCM, GPCM and the GRM reflected the discrimination parameter estimates for the latter two models. Suggestions are made with regard to model selection.

Aptitude Tests↗

PubMed2004

Estimation of surface pose with a physically-based ultrasonic image model.

State-of-the-art approaches to shape analysis in medical images use a variety of sophisticated models for object shape. We have developed an image model that permits the application of these approaches to ultrasonic images, with detailed methods for representing rough surfaces. Our physically-based, probabilistic image model incorporates the combined effects of the system point-spread function (PSF), the tissue microstructure, and the gross tissue shape. At each image pixel, the amplitude mean and variance are computed directly from the model, characterizing the combined influence of shape, microstructure, and system PSF. Calculation of the SNR0 is used to further classify each pixel as Rayleigh- or non-Rayleigh-distributed. This characterization was used here to generate a data likelihood representing any set of images of a given surface by a probability density conditioned on the surface pose, or rotation and translation. The utility of this likelihood was demonstrated by applying maximum likelihood estimation to infer the pose of a cadaveric vertebra from simulated images of its surface. Successful results were achieved using derivative-based optimization algorithms for a data set of only three images. With a quasi-Newton BFGS algorithm, error in 15 of 20 trials was less than 0.4 degrees in rotation and 0.2 mm in translation. Estimation was inaccurate in only 1 of 20 trials. These results illustrate the potential of a physically-based image model in a rigorous approach to image analysis and also serve as an example of quantitative assessment of the model via performance in a specific application.

Algorithms↗

PubMed2002

Modeling multivariate survival data by a semiparametric random effects proportional odds model.

In this article, the focus is on the analysis of multivariate survival time data with various types of dependence structures. Examples of multivariate survival data include clustered data and repeated measurements from the same subject, such as the interrecurrence times of cancer tumors. A random effect semiparametric proportional odds model is proposed as an alternative to the proportional hazards model. The distribution of the random effects is assumed to be multivariate normal and the random effect is assumed to act additively to the baseline log-odds function. This class of models, which includes the usual shared random effects model, the additive variance components model, and the dynamic random effects model as special cases, is highly flexible and is capable of modeling a wide range of multivariate survival data. A unified estimation procedure is proposed to estimate the regression and dependence parameters simultaneously by means of a marginal-likelihood approach. Unlike the fully parametric case, the regression parameter estimate is not sensitive to the choice of correlation structure of the random effects. The marginal likelihood is approximated by the Monte Carlo method. Simulation studies are carried out to investigate the performance of the proposed method. The proposed method is applied to two well-known data sets, including clustered data and recurrent event times data.

Animals↗

PubMed2004

Habitat and home range fidelity in a trophically dimorphic pumpkinseed sunfish (Lepomis gibbosus) population.

We investigated habitat selection in a trophically dimorphic population of pumpkinseed sunfish (Lepomis gibbosus) to determine whether littoral and limnetic ecotypes exhibit habitat or site fidelity. A transplant experiment was conducted, in which 998 pumpkinseeds captured from littoral and limnetic sites were marked and released in either the site of capture, the nearest site of the same habitat type, or the nearest site of the opposite habitat type. Daily recapture attempts over the course of the reproductive and growing season provided a 25% recapture rate, 40% of which were recaptured on multiple occasions at the same site. Site fidelity was very high in both ecotypes. Results estimated with a multi-state transition model indicated that the probability of a transplanted pumpkinseed returning to its site of origin ranged from 74% for limnetic pumpkinseeds released into a different limnetic or littoral site, to 93% for littoral pumpkinseeds released into a limnetic site. Furthermore, the probability of a pumpkinseed being recaptured at its site of origin if not transplanted was estimated at 97 and 98% for limnetic individuals and littoral individuals, respectively. Discriminant Function Analysis of helminth parasite loads sampled from littoral and limnetic individuals could classify site of origin with 96-100% accuracy, suggesting that the habitat and site fidelity patterns observed with mark-recapture are indicative of long-term habitat segregation of the two forms. The results of our experiment provide compelling evidence of correlated habitat selection as a function of home range fidelity within both ecotypes of a subtly dimorphic species. Such behaviour could have a significant effect on present or future gene flow.

Animals↗

PubMed1994

Handling covariates in population pharmacokinetics.

Population models were developed to analyze processes, described by parametric models, from measurements obtained in a sample of individuals. In order to analyze the sources of interindividual variability, covariates may be incorporated in the population analysis. The exploratory analyses and the two-stage approaches which use standard non-linear regression techniques are simple tools to select meaningful covariates. The global population approaches may be divided into two classes within which the covariates are handled differently: the parametric and the non-parametric methods. The power as well as the limitations of each approach regarding handling of covariates are illustrated and compared using the same data set which concerns the pharmacokinetics of gentamicin in neonates. With parametric approaches a second-stage model between structural parameters and covariates has to be defined. In the non-parametric method the joint distribution of parameters and covariates is estimated without parametric assumptions; however, it is assumed that covariates are observed with some error and parameters involved in functional relationships are not estimated. The important results concerning gentamicin in neonates were found by the two methods.

Age Factors↗

PubMed2005

Detecting and adjusting for artifacts in fMRI time series data.

We present a new method to detect and adjust for noise and artifacts in functional MRI time series data. We note that the assumption of stationary variance, which is central to the theoretical treatment of fMRI time series data, is often violated in practice. Sporadic events such as eye, mouth, or arm movements can increase noise in a spatially global pattern throughout an image, leading to a non-stationary noise process. We derive a restricted maximum likelihood (ReML) algorithm that estimates the variance of the noise for each image in the time series. These variance parameters are then used to obtain a weighted least squares estimate of the regression parameters of a linear model. We apply this approach to a typical fMRI experiment with a block design and show that the noise estimates strongly vary across different images and that our method detects and appropriately weights images that are affected by artifacts. Furthermore, we show that the noise process has a global spatial distribution and that the variance increase is multiplicative rather than additive. The new algorithm results in significantly increased sensitivity in the ability to detect regions of activation. The new method may be particularly useful for studies that involve special populations (e.g., children or elderly) where sporadic, artifact-generating events are more likely.

Algorithms↗

PubMed1996

Sensitivity, specificity, and predictive values of screening tests for eye conditions in a clinic-based population.

PURPOSE: To assess four commonly available visual function tests to detect visually disabling or vision-threatening eye conditions among new patients of a large, urban, public, general ophthalmology clinic. METHODS: Three hundred seventeen patients were tested for contrast sensitivity, Amsler grid abnormalities, and visual acuity at near and at distance. A complete eye evaluation found the prevalence of serious eye diseases, allowing determination of the sensitivity (Sn), specificity (Sp), likelihood ratio (LR), and other characteristics of each test. RESULTS: Of 317 patients, most were Hispanic (77%), women (60%), and middle-aged (44 +/- 17 years). Normal findings were reported in 18%; refractive error in 43%; cataracts in 16%; glaucoma in 7.3%; and macular degeneration in 4.1%. Near visual acuity of 20/40 or worse (Sn = 0.75; Sp = 0.74; LR = 2.8); and distance visual acuity testing of 20/30 or worse (Sn = 0.74; Sp = 0.73; LR = 2.7) correlated significantly with ocular disease, whereas contrast sensitivity testing (Sn = 0.62; Sp = 0.41; LR = 1.1) and Amsler grid test (Sn = 0.19; Sp = 0.92; LR = 2.4) did not. Test performance decreased when refractive errors were excluded and among those younger than 40 years of age relative to those 40 years of age or older. CONCLUSION: Of the four screening tests studied, distance and near threshold visual acuities as defined above were judged to have the best correlations of an abnormal result with ocular disease, both including or excluding refractive error. Different combinations of tests did not result in more accurate detection of ocular disease. More efficient screening tools for detecting ocular disease need to be developed.

Adolescent↗

PubMed1993

An assessment of survival rates and within-patient clustering of failures for endosseous oral implants.

This study examined endosseous cylinder implant survival, defined as the unqualified presence of the implant in the mouth at the end of the observation period, in 598 consecutive VA patients, with a total of 2098 implants. Data were taken from the Department of Veterans Affairs (VA) Dental Implant Registry, which has maintained longitudinal data on the survival of individual dental implants in VA patients since 1987. The maximum time of observation in any one patient was 2040 days (5.6 yr). Survival analysis by use of life-table methods was carried out on both an implant- and a patient-specific basis. Implant cases were accrued randomly, and therefore a random censoring model was used. A correlated binomial model was used for assessment of the degree of within-patient clustering of implant removals. Results showed that the implant-specific survival rate during the longest time interval (5.6 yr) was 89.9%; the patient-specific implant survival rate during the same time was 78.2%. Among implants which were removed, the mean time to removal was 292 days. The hazard function, which describes the probability of implant loss as a function of time, decreased steadily throughout the observation period. The correlated binomial model suggested a clustering of removals within patients with multiple implants (rho = 0.11, p = 0.0001). The odds of having a second implant removed were 1.3 times greater if the patient had already had one implant removed. This study suggests that when implants fail, they do so soon after placement, and the likelihood of failure decreases steadily from implantation through the first five years post-surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

A multivariate logistic model (MLM) for analyzing binary family data.

We consider modeling the familial correlation between 2 related individuals using a multiple logistic regressive model. It is shown that there is a discrepancy in the marginal probability of the second individual. We investigate the conditions under which this discrepancy can be minimized and show how it can have a direct effect on handling missing values and ascertainment. We derive a functional relationship between the parameters in the model that eliminates this discrepancy, hence solving the problems that can arise in the handling of missing values and ascertainment. Because this methodology fails when there are more than 2 related individuals, we present a new model based on a multivariate logistic distribution. Residual familial correlations can be directly related to the parameters of this model. The likelihood for family data under this model is independent of the order in which the family members enter the calculation. The marginal probabilities can be easily computed.

Data Interpretation, Statistical↗

PubMed1995

Statistical methods for dependent competing risks.

Many biological and medical studies have as a response of interest the time to occurrence of some event, X, such as the occurrence of cessation of smoking, conception, a particular symptom or disease, remission, relapse, death due to some specific disease, or simply death. Often it is impossible to measure X due to the occurrence of some other competing event, usually termed a competing risk. This competing event may be the withdrawal of the subject from the study (for whatever reason), death from some cause other than the one of interest, or any eventuality that precludes the main event of interest from occurring. Usually the assumption is made that all such censoring times and lifetimes are independent. In this case one uses either the Kaplan-Meier estimator or the Nelson-Aalen estimator to estimate the survival function. However, if the competing risk or censoring times are not independent of X, then there is no generally acceptable way to estimate the survival function. There has been considerable work devoted to this problem of dependent competing risks scattered throughout the statistical literature in the past several years and this paper presents a survey of such work.

Data Interpretation, Statistical↗

PubMed2004

Archaeal community structure and pathway of methane formation on rice roots.

The community structure of methanogenic Archaea on anoxically incubated rice roots was investigated by amplification, sequencing, and phylogenetic analysis of 16S rRNA and methyl-coenzyme M reductase (mcrA) genes. Both genes demonstrated the presence of Methanomicrobiaceae, Methanobacteriaceae, Methanosarcinaceae, Methanosaetaceae, and Rice cluster I, an uncultured methanogenic lineage. The pathway of CH4 formation was determined from the 13C-isotopic signatures of the produced CH4, CO2 and acetate. Conditions and duration of incubation clearly affected the methanogenic community structure and the pathway of CH4 formation. Methane was initially produced from reduction of CO2 exclusively, resulting in accumulation of millimolar concentrations of acetate. Simultaneously, the relative abundance of the acetoclastic methanogens (Methanosarcinaceae, Methanosaetaceae), as determined by T-RFLP analysis of 16S rRNA genes, was low during the initial phase of CH4 production. Later on, however, acetate was converted to CH4 so that about 40% of the produced CH4 originated from acetate. Most striking was the observed relative increase of a population of Methanosarcina spp. (but not of Methanosaeta spp.) briefly before acetate concentrations started to decrease. Both acetoclastic methanogenesis and Methanosarcina populations were suppressed by high phosphate concentrations, as observed under application of different buffer systems. Our results demonstrate the parallel change of microbial community structure and function in a complex environment, i.e., the increase of acetoclastic Methanosarcina spp. when high acetate concentrations become available.

Acetates↗

PubMed2001

GeneMarkS: a self-training method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions.

Improving the accuracy of prediction of gene starts is one of a few remaining open problems in computer prediction of prokaryotic genes. Its difficulty is caused by the absence of relatively strong sequence patterns identifying true translation initiation sites. In the current paper we show that the accuracy of gene start prediction can be improved by combining models of protein-coding and non-coding regions and models of regulatory sites near gene start within an iterative Hidden Markov model based algorithm. The new gene prediction method, called GeneMarkS, utilizes a non-supervised training procedure and can be used for a newly sequenced prokaryotic genome with no prior knowledge of any protein or rRNA genes. The GeneMarkS implementation uses an improved version of the gene finding program GeneMark.hmm, heuristic Markov models of coding and non-coding regions and the Gibbs sampling multiple alignment program. GeneMarkS predicted precisely 83.2% of the translation starts of GenBank annotated Bacillus subtilis genes and 94.4% of translation starts in an experimentally validated set of Escherichia coli genes. We have also observed that GeneMarkS detects prokaryotic genes, in terms of identifying open reading frames containing real genes, with an accuracy matching the level of the best currently used gene detection methods. Accurate translation start prediction, in addition to the refinement of protein sequence N-terminal data, provides the benefit of precise positioning of the sequence region situated upstream to a gene start. Therefore, sequence motifs related to transcription and translation regulatory sites can be revealed and analyzed with higher precision. These motifs were shown to possess a significant variability, the functional and evolutionary connections of which are discussed.

Algorithms↗

PubMed2000

New target regions for human hypertension via comparative genomics.

Models of human disease have long been used to understand the basic pathophysiology of disease and to facilitate the discovery of new therapeutics. However, as long as models have been used there have been debates about the utility of these models and their ability to mimic clinical disease at the phenotypic level. The application of genetic studies to both humans and model systems allows for a new paradigm, whereby a novel comparative genomics strategy combined with phenotypic correlates can be used to bridge between clinical relevance and model utility. This study presents a comparative genomic map for "candidate hypertension loci in humans" based on translating QTLs between rat and human, predicting 26 chromosomal regions in the human genome that are very likely to harbor hypertension genes. The predictive power appears robust, as several of these regions have also been implicated in mouse, suggesting that these regions represent primary targets for the development of SNPs for linkage disequilibrium testing in humans and/or provide a means to select specific models for additional functional studies and the development of new therapeutics.

Animals↗

PubMed2004

Erosion of regression effect in a survival study.

Lack of persistence, or erosion, of the regression effect is an alternative to proportional hazards of particular interest in many medical applications. Such a departure from proportional hazards is often the most likely direction in which the model may be inadequate. Questions such as, is the effect of treatment only transitory or to what extent does an initially measured prognostic variable maintain its impact, frequently arise. In the context of a simple changepoint model, we propose a test of the null hypothesis of proportional hazards against the specific alternative of erosion of the regression effect. The particular changepoint model used can be viewed as a first approximation to a more complex reality, an approximation that enables us to avoid specifically modeling the functional form that any erosion might take. Practical guidelines for carrying out the test are provided. The approach is illustrated in the context of a study on risk factors for breast cancer survival.

Biometry↗